CroSR391, an ortholog of the λ Cro repressor, plays a major role in suppressing polVR391‐dependent mutagenesis. Issue 3 (12th July 2021)

• Record Type: Journal Article
• Authors: McDonald, John P.; Quiros, Dominic R.; Vaisman, Alexandra; Mendez, Antonio R.; Reyelt, Jan; Schmidt, Marlen; Gonzalez, Martín; Woodgate, Roger
• Is Part Of: Molecular microbiology. Volume 116:Issue 3(2021)
• Page Start: 877
• Page End: 889
• Publication Date: 2021-07-12
• Subjects: DNA polymerase V -- integrating conjugative element -- mutagenesis -- R391 -- SOS response; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14777
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: When subcloned into low‐copy‐number expression vectors, rumAB, encoding polVR391 (RumA′2 B), is best characterized as a potent mutator giving rise to high levels of spontaneous mutagenesis in vivo . This is in dramatic contrast to the poorly mutable phenotype when polVR391 is expressed from the native 88.5 kb R391, suggesting that R391 expresses cis ‐acting factors that suppress the expression and/or the activity of polVR391 . Indeed, we recently discovered that SetRR391, an ortholog of λ cI repressor, is a transcriptional repressor of rumAB . Here, we report that CroSR391, an ortholog of λ Cro, also serves as a potent transcriptional repressor of rumAB . Levels of RumA are dependent upon an interplay between SetRR391 and CroSR391, with the greatest reduction of RumA protein levels observed in the absence of SetRR391 and the presence of CroSR391 . Under these conditions, CroSR391 completely abolishes the high levels of mutagenesis promoted by polVR391 expressed from low‐copy‐number plasmids. Furthermore, deletion of croS R391 on the native R391 results in a dramatic increase in mutagenesis, indicating that CroSR391 plays a major role in suppressing polVR391 mutagenesis in vivo . Inactivating mutations in CroSR391 therefore have the distinct possibility of increasing cellular mutagenesis that could lead to the evolution of antibiotic resistance of pathogenic bacteria harboring R391. Abstract : When subcloned from R391 into low‐copy‐number expression vectors, polVR391 (RumA′2 B) encoded by rumAB, is a potent mutator giving rise to high levels of spontaneous mutagenesis in vivo. This is in contrast to the poorly mutable phenotype when polVR391 is expressed from the native R391. Here, we report that CroSR391, an ortholog of λ Cro, serves as a potent transcriptional repressor of rumAB that plays a major role in suppressing polVR391 mutagenesis in vivo .